Globular Proteins

Most proteins which occur in the aqueous, intracellular environment or in
the plasma are
of globular nature: they are very approximately spherical in shape, or consist
of several different lobes (domains). Generally,
proteins with more than about 200 amino acid residues are multi-domain (although
there are exceptions). The different domains of a single protein may be responsible
for quite different functions. This is taken to extremes in a number of 'modular'
proteins, which are mostly extracellular and glycosylated (see section on
mosaic proteins).

The tertiary structure of globular proteins reflects their interaction with their
aqueous solvent. At a simple level, a globular protein may be considered to
consist of a hydrophobic core surrounded by a hydrophilic external surface which
interacts with water. The tertiary fold of the polypeptide is such that those
residues with apolar side chains are buried in the centre, while the polar
residues remain exposed. This principle is held by many to be the dominant
driving force behind the folding of the polypeptide chain into the compact
globular form:
the aggregation and burial of the hydrophobic surface reduces the number of
unfavourable interactions of these groups with water; thus the hydrophobic
effect. (A section on this will be released in due course.)

Compare this distribution of hydrophilic and hydrophobic side chains with that
in an integral membrane protein (see the relevant
page).

Bear in mind however that although the concept of "hydrophobic residues in,
polar residues out" generally applies, it has its limitations.
Residues with hydrophobic side chains have some polar surface area (the backbone
atoms), and vice versa.
There will necessarily be some buried polar groups in the hydrophobic
interior (generally main chain atoms involved in hydrogen bonding in secondary
structures). Likewise, the amount of solvent-exposed hydrophobic surface area
is far more than minimal: in fact it constitutes approximately 50% of the
total exposed surface area of a globular protein.
A patchwork arrangement of hydrophobic and polar surface
allows solvent molecules close to apolar regions to interact favourably
with neighbouring polar surfaces.